Central adrenal insufficiency screening with morning plasma cortisol and ACTH levels in Prader-Willi syndrome

Abstract

Objectives: Prader-Willi syndrome (PWS) is a complex genetic disorder with severe hypotonia, failure to thrive, childhood obesity, hypogonadism/hypogenitalism and learning/behavioral problems with endocrine-related growth and other hormone deficiencies. The prevalence of central adrenal insufficiency (CAI) using dynamic testing ranges from rare to 60%. We compared routine morning plasma cortisol (MPC) and ACTH levels in large cohorts of PWS and control children to address CAI.

Methods: Retrospective analysis of MPC and ACTH levels was undertaken in 128 PWS growth hormone (GH)-treated children under medical care before considering dynamic testing for CAI and 128 non-syndromic control children with short stature evaluated for GH deficiency.

Results: The average MPC level in PWS was 9.7 ± 3.7 μg/dL with no difference in age, gender or PWS genetic subtype and 13.4 ± 5.7 μg/dL in the control group. MPC levels were significantly lower (p < 0.05) in PWS but in the normal range. The morning plasma ACTH level in the PWS group was 22.1 ± 8.0 pg/mL with one individual having an initial low plasma ACTH level (8 pg/mL), but normal upon repeat.

Conclusions: MPC levels in PWS are normal and comparable with control children, without evidence or increased risk of CAI. Lower but normal MPC levels were seen in PWS and suggestive of reduced local regeneration of cortisol from cortisone in adipose tissue by the GH-IGF-I system. Hence, MPC measures alone or in combination with ACTH should be considered for initial screening for CAI in PWS but prior to dynamic testing.

Keywords: Prader–Willi syndrome; adrenal insufficiency; dynamic testing; growth hormone; plasma cortisol and ACTH levels.